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Spatial planning deficits in limb apraxia.

Geschwind (1975) proposed a disconnection model in which an apraxic subject is unable to carry out movements to command because the left hemisphere that comprehended the verbal command is disconnected from the right premotor and motor areas which controls the left hand. An alternate model, however, proposes that apraxia results from destruction of spatiotemporal representations of learned movement stored in the left hemisphere (Heilman, 1979). The disconnection hypothesis would predict that apraxic subjects should be able to correctly imitate gestures and correctly use actual tools since these tasks do not require language. The movement representation model predicts that imitation and actual tool use would also be impaired. Motion analyses were performed on the trajectories of repetitive 'slicing' gestures made in a series of conditions in which contextual cues were introduced in a graded fashion. Four cue conditions were presented: no cues (verbal command), object present, tool present and both object and tool present. Positions of the hand, wrist, elbow, and shoulder were digitized from neighbouring views, reconstructed in three dimensions and analysed with respect to specific spatiotemporal features of the trajectories. Three subjects with limb apraxia, who had lesions that included left parietal cortex, and four neurologically intact subjects participated. The apraxic subjects showed disturbances in planning the movement of the hand in space across the cue conditions. For example, they showed deficits in the plane of motion, the shape of the trajectory and in the coupling of hand speed and trajectory shape even when given full contextual cues. These data support the hypothesis that apraxia can result from the destruction of spatiotemporal representations of learned movement, rather than from a disconnection between the receptive language areas in the left hemisphere and the contralateral motor cortices.

Aged↗

Random matrix approach to multivariate correlations: some limiting cases.

Recent advances have shown that the empirical correlation matrices of dynamical systems can be modeled as random matrices, for most part, chosen from an appropriate ensemble of the random matrix theory (RMT). In this work, we study certain limiting cases where this approach could potentially break down. Using a combination of analytical and numerical tools, we especially study the eigenvalue density and its spacing distribution. We show that the correlation matrices obtained from multivariate spatiotemporal timeseries, in a regime of spatiotemporal chaos, lead to strong deviations from RMT. We illustrate the results with time-series data drawn from coupled map lattices. We also explore the transition to the RMT regime from the limiting cases.

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Collective directed transport of symmetrically coupled lattices in symmetric periodic potentials.

A mechanism responsible for the directed transport of symmetrically coupled lattices in a symmetric periodic potential is proposed. Under the action of an external wave that breaks the spatiotemporal symmetry and introduces inhomogeneities of the lattice, a net unidirectional current can be observed, originating from a collaboration of the lattice (periodic potential and mutual interactions) and the wave (amplitude, frequency, and phase shifts). Mode-locking induced resonant steps are observed and predicted. The directed transport can be optimized and furthermore controlled by suitably adjusting the parameters of the system.

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A photoactivatable Cre-loxP system for spatiotemporal genetic manipulation in mouse taste buds.

Conventional genetic approaches, including global gene KO and conditional KO strategies such as the Cre-loxP system, have some limitations arising from systemic effects or insufficient temporal resolution. The recently developed photoactivatable Cre (PA-Cre) system may have a potential to improve spatiotemporal control of gene manipulation. In this study, we established and validated the feasibility of the PA-Cre system using taste buds as a model. We generated TRE-PA-Cre:R26-rtTA/tdTomato mice to evaluate blue-light-induced Cre recombinase activity. Through systematic optimization of illumination parameters, we found that a single session of blue-light-illumination resulted in limited recombination efficiency, whereas a multisession illumination strategy markedly increased recombination efficiency. To further assess the utility of the PA-Cre system for gene KO, we generated TRE-PA-Cre:R26-rtTA:Tas1r3-flox mice and targeted a taste-related gene Tas1r3. Genomic DNA quantitative PCR and reverse transcription-quantitative PCR both showed partial reductions in Tas1r3 at the DNA and mRNA levels, respectively. Behavioral assays further revealed a selective decrease in sensitivity to sweet and umami stimuli. Together, these findings demonstrate PA-Cre-mediated gene manipulation in taste buds and establish a practical optical activation paradigm, providing a high-spatiotemporal-resolution tool for investigating gene function in optically targeted regions.

Animals↗

Spatiotemporal quantification of cerebral blood flow during functional activation in rat somatosensory cortex using laser-speckle flowmetry.

Laser-speckle flowmetry was used to characterize activation flow coupling after electrical somatosensory stimulation of forepaw and hindpaw in the rat. Quantification of functional activation was made with high transverse spatial (microm) and temporal (msec) resolution. Different activation levels and duration of stimulation were quantitatively investigated, and were in good agreement with previous laser-Doppler measurements. Interestingly, the magnitude but not the overall shape of the response was found to scale with stimulus amplitude and the distance from the activation centroid. The results provide new insights about the spatial characteristics of cerebral blood flow response to functional activation, and the method should lead to improved understanding of the coupling of neuronal activity and hemodynamics under normal and pathologic conditions.

Animals↗

Spatiotemporal digital microholography.

We develop the theoretical background of a holographic method in which the hologram is sampled simultaneously in space and in time by a charge-coupled device (CCD) sensor. With the use of temporal heterodyning (rather than spatial heterodyning, which is employed in conventional holography), in-line, single-sideband holograms of fields having an arbitrary degree of spatial coherence are recorded in an exposure time that can theoretically be as short as four frames of the CCD. The method is applied to microholography and is shown to avoid the main drawbacks of conventional holographic microscopy, namely, the need for high-spatial-bandwidth detectors and for a high degree of spatial coherence, which unavoidably leads to speckle noise. The possibility of a posteriori aberration compensation is demonstrated, and experimental results are presented.

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Spatiotemporal testing and modeling of catfish retinal neurons.

The responses of retinal neurons depend on the interaction of both temporal and spatial aspects of a light stimulus. We developed a linear spatiotemporal model of receptor and horizontal cell layers in the catfish retina based on reciprocal interactions between both layers and coupling within each. Horizontal cell transfer properties were measured experimentally using white-noise intensity modulated light spots of different diameters and were compared with analytical predictions based on the model. Good agreement was obtained with a reasonable choice of model space-constants and feedback parameters. Furthermore, the same set of parameter values determined from spot experiments enabled accurate prediction of experimental horizontal cell responses to traveling gratings. The proposed feedback connections from horizontal cells to receptors quicken the time-course of responses in both layers and sharpen receptive fields.

Animals↗

The spatial logistic map as a simple prototype for spatiotemporal chaos.

A spatial extension of the logistic map-termed spatial logistic map-is found to display the same basic universality classes as the commonly studied diffusively coupled logistic lattice despite being vastly simpler. By analyzing the escape rates and the Lyapunov spectra it is shown that the main attractors of the spatial logistic map are stable and hence that it is a good candidate for serving as a prototype for the class of coupled map lattices which it is a part of. The spatial logistic map is then employed to provide an analytical derivation for the recently discovered linear scaling of the wavelength under increasing coupling ranges.

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Spatiotemporal oscillations and rheochaos in a simple model of shear banding.

We study a simple model of shear banding in which the flow-induced phase is destabilized by coupling between flow and microstructure (wormlike micellar length). By varying the strength of instability and the applied shear rate, we find a rich variety of oscillatory and chaotic shear banded flows. At low shear and weak instability, the induced phase pulsates next to one wall of the flow cell. For stronger instability, high shear pulses ricochet across the cell. At high shear we see oscillating bands on either side of central defects. We discuss our results in the context of recent experiments.

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Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors.

Hirschsprung disease (HSCR) is a multigenic, congenital disorder that affects 1 in 5,000 newborns and is characterized by the absence of neural crest-derived enteric ganglia in the colon. One of the primary genes affected in HSCR encodes the G protein-coupled endothelin receptor-B (EDNRB). The expression of Ednrb is required at a defined time period during the migration of the precursors of the enteric nervous system (ENS) into the colon. In this study, we describe a conserved spatiotemporal ENS enhancer of Ednrb. This 1-kb enhancer is activated as the ENS precursors approach the colon, and partial deletion of this enhancer at the endogenous Ednrb locus results in pigmented mice that die postnatally from megacolon. We identified binding sites for SOX10, an SRY-related transcription factor associated with HSCR, in the Ednrb ENS enhancer, and mutational analyses of these sites suggested that SOX10 may have multiple roles in regulating Ednrb in the ENS.

Animals↗

Implication of nNOS in the enlargement of AChR aggregates but not the initial aggregate formation in a novel coculture model.

The aggregation of nicotinic acetylcholine receptors (AChRs) is an early hallmark of the formation of neuromuscular junction (NMJ), and nitric oxide is recently known to play an important role. In many NMJ studies, nerve-muscle coculture model was used, and NG108-15 cells, a neuroblastoma x glioma hybrid cell line, were the most frequently used nerve cells. However, possible contributions from glial cells could not be excluded. In this study, Neuro-2a neuroblastoma cells were used instead of [corrected] coculture with myotubes, and the relationship between AChR aggregation and spatiotemporal expression and activation of nNOS (neuronal nitric oxide synthase) was examined. Upon coculture, AChR aggregates were observed by FITC-conjugated alpha-bungarotoxin, and double labeling of AChRs and neurofilament showed that the neurites of a Neuro-2a cell innervated several myotubes. After treating the cocultures with single dose of L-NAME at the end of 1-day [corrected] coculturing, only slight effect on AChR aggregation could be found indicating that nNOS is not related to the initial formation of AChR aggregates. In contrast, when L-NAME treatment was given at the end of a 3-day coculturing, the day just before reaching the maximum extent of AChR aggregation, new AChR aggregates were hardly formed and the preformed AChR aggregates were even dispersed indicating that the enlargement of AChR aggregates is highly dependent on the nNOS activity. Double-labeling study of nNOS and AChR further showed that the coupling of membranous nNOS to regions nearby the AChR aggregates was essential for the enlargement of AChR aggregates. These results not only revealed the spatiotemporal relationship between AChR aggregation and nNOS activity but also verified the feasibility and usefulness of using Neuro-2a cells in a coculture model.

Animals↗

Regimes of biological invasion in a predator-prey system with the Allee effect.

Spatiotemporal dynamics of a predator-prey system is considered under the assumption that prey growth is damped by the strong Allee effect. Mathematically, the model consists of two coupled diffusion-reaction equations. The initial conditions are described by functions of finite support which corresponds to invasion of exotic species. By means of extensive numerical simulations, we identify the main scenarios of the system dynamics as related to biological invasion. We construct the maps in the parameter space of the system with different domains corresponding to different invasion regimes and show that the impact of the Allee effect essentially increases the system spatiotemporal complexity. In particular, we show that, as a result of the interplay between the Allee effect and predation, successful establishment of exotic species may not necessarily lead to geographical spread and geographical spread does not always enhance regional persistence of invading species.

Algorithms↗

Acetylcholine-induced calcium signaling along the rat colonic crypt axis.

BACKGROUND & AIMS: Acetylcholine-induced calcium signaling dynamics have been described in cell monolayers derived from colonic mucosa, but not in intact colonic crypts. The aim of this study was to characterize the spatiotemporal characteristics of calcium signaling induced by acetylcholine in isolated intact rat colonic crypts and to identify the muscarinic receptor subtype coupled to this signaling pathway. METHODS: Isolated crypts from the distal colon of male Wistar rats were loaded with the calcium-sensitive dye Fura-2 and imaged with a charge-coupled device video camera. RESULTS: Acetylcholine mobilized intracellular calcium with an EC50 of 3.9 micromol/L. The response was initiated at the base of the crypt and progressed toward the surface. The velocity of propagation was dose dependent. Addition of muscarinic antagonists inhibited the response (pKb values calculated for pirenzepine and 4-DAMP, 6.08 and 8.65, respectively). Microperfusion of acetylcholine initiated a calcium signal throughout the lower half of the crypt. Microinjection of inositol 1,4,5-triphosphate induced a propagation of a calcium signal along the crypt axis. Heptanol inhibited the velocity of acetylcholine-induced wave propagation by 33%. CONCLUSIONS: M3 muscarinic receptors are coupled to the mobilization of calcium from intracellular stores of intact, isolated rat colonic crypts. Intercellular communication potentiates the propagation of the acetylcholine-induced calcium signal along the crypt axis.

Acetylcholine↗

Images of Action Potential Propagation in Heart.

Activation and repolarization across mammalian hearts follow complex three-dimensional pathways that are governed by fiber structure, intercellular coupling, and action potentials (APs) with spatially heterogeneous properties. Voltage-sensitive dyes and imaging techniques offer new insights on how spatiotemporal heterogeneities of APs govern propagation, repolarization, and AV node conduction and help us visualize arrhythmias with previously unattainable details.

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Practical realization of high-speed photodisplacement imaging by use of parallel excitation and parallel heterodyne detection: a numerical study.

A new parallel photodisplacement technique that achieves extremely high-throughput imaging is proposed, and its practical realization is studied numerically. In this technique, a linear region of photothermal displacement is excited by use of a line-focusing intensity-modulated laser beam and detected with a parallel heterodyne interferometer in which a charge-coupled device linear image sensor is used. Because of the integration and sampling effects of the sensor, the interference light is spatiotemporally multiplexed. To extract the photodisplacement component from the multiplexed sensor signal, a scheme of phase-shifting light integration under an undersampling condition is proposed for parallel interferometry. The frequencies of several control signals, including the heterodyne beat signal, modulation signal, and sensor gate signal, are optimized so as to eliminate undesirable components, allowing only the displacement component to be extracted. Preliminary numerical simulation results show that the proposed technique has the potential to perform photodisplacement imaging more than 10,000 times faster than conventional photoacoustic microscopy.

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Plankton lattices and the role of chaos in plankton patchiness.

Spatiotemporal and interspecies irregularities in planktonic populations have been widely observed. Much research into the drivers of such plankton patches has been initiated over the past few decades but only recently have the dynamics of the interacting patches themselves been considered. We take a coupled lattice approach to model continuous-in-time plankton patch dynamics, as opposed to the more common continuum type reaction-diffusion-advection model, because it potentially offers a broader scope of application and numerical study with relative ease. We show that nonsynchronous plankton patch dynamics (the discrete analog of spatiotemporal irregularity) arise quite naturally for patches whose underlying dynamics are chaotic. However, we also observe that for parameters in a neighborhood of the chaotic regime, smooth generalized synchronization of nonidentical patches is more readily supported which reduces the incidence of distinct patchiness. We demonstrate that simply associating the coupling strength with measurements of (effective) turbulent diffusivity results in a realistic critical length of the order of 100 km, above which one would expect to observe unsynchronized behavior. It is likely that this estimate of critical length may be reduced by a more exact interpretation of coupling in turbulent flows.

Animals↗

mGluR2 postsynaptically senses granule cell inputs at Golgi cell synapses.

In the cerebellar circuit, Golgi cells are thought to contribute to information processing and integration via feedback mechanisms. In these mechanisms, dynamic modulation of Golgi cell excitability is necessary because GABA from Golgi cells causes tonic inhibition on granule cells. We studied the role and synaptic mechanisms of postsynaptic metabotropic glutamate receptor subtype 2 (mGluR2) at granule cell-Golgi cell synapses, using whole-cell recording of green fluorescent protein-positive Golgi cells of wild-type and mGluR2-deficient mice. Postsynaptic mGluR2 was activated by glutamate from granule cells and hyperpolarized Golgi cells via G protein-coupled inwardly rectifying K+ channels (GIRKs). This hyperpolarization conferred long-lasting silencing of Golgi cells, the duration and extents of which were dependent on stimulus strengths. Postsynaptic mGluR2 thus senses inputs from granule cells and is most likely important for spatiotemporal modulation of mossy fiber-granule cell transmission before distributing inputs to Purkinje cells.

Animals↗

Cerebellar subjects show impaired coupling of reach and grasp movements.

We examined how cerebellar deficits in isolated reaching or grasping movements contribute to abnormalities in a combined reach and grasp movement, and whether people with cerebellar damage show abnormalities in the spatiotemporal relationships of reach and grasp movements. We studied subjects with cerebellar damage and matched controls as they performed a combined reach and grasp, an isolated reach, and an isolated grasp. These movements were performed under slow-accurate and fast speed conditions. Subjects were also tested for their ability to correctly estimate the target size based on visual information. We measured the three-dimensional position of the index finger, thumb and wrist joint during all tasks. Results showed that cerebellar subjects overestimated the target size to a greater extent than did controls. During movement testing, cerebellar subjects were impaired on isolated reach and isolated grasp. However, they did not worsen parameters of reach or grasp movements during the combined reach and grasp. Instead there were distinct deficits in the coupling of the reach and grasp movement. Compared with controls, cerebellar subjects showed abnormalities in the sequence of the reach and grasp movement and highly variable timing of peak grip aperture. In the slow-accurate condition, cerebellar subjects decomposed the reach and grasp movement into separate reach then grasp components, and produced multiple peaks in grip aperture. In the fast condition, cerebellar subjects did not decompose, produced a single peak grip aperture, and dropped the target more often. These results indicate that cerebellar damage can cause a specific breakdown in the coupling of reach and grasp movements. The cerebellum may be involved in combining reach and grasp movements into a single motor program.

Adult↗